This proposal requests a new state of the art high performance positron emission tomography (PET) scanner to replace the GE Advance whole body scanner currently used in our PET center. The new scanner will be dedicated to greatly enhanced human brain imaging, pre-clinical studies of the CNS, and pre-clinical studies from other disciplines, including cancer. Our funded and pending research studies encompass multiple universities, institutes, and schools within and outside Johns Hopkins University including international collaborations. Imaging of non human primate and human CNS neuro-receptors has been the major focus of our previous research, with studies of groups including: children with mental retardation, young adults with schizophrenia, depression, and substance abuse, and diseases in the elderly, including depression, and Parkinson's Disease. A major program of public health and medical significance involves studies of neuro-toxicity. All of these studies require exquisite 3-D resolution sensitivity axial sampling to provide the maximum recovery of radiotracer binding to small structures. Our research plan has four major areas: brain imaging and substance abuse (including alcohol and cocaine), mental illnesses (including schizophrenia and depression), neurological and developmental disorders, and pre-clinical studies for radioligand development in cancer and the CNS. Almost 30 currently funded NIH grants including RO1's, program projects, and center grants, are represented in this application. The scientific scope of our PET program and the number of investigators involved has increased dramatically over the past several years. With many new radiotracers available and increased interest in pre-clinical pharmaceutical collaboration, the opportunities for multiple receptor radiotracers for brain imaging is a reality. These measurements cannot be reproduced by any other methodology with the same degree of quantification, sensitivity, or specificity. These studies go beyond pathophysiology to include drug development and treatment monitoring of neuro-psychiatric disorders. As more is known about brain neurochemistry, the demands for imaging smaller and more intricate structures becomes increasingly important. The new high performance PET camera with advanced crystal designs, larger bore size, and great improvements in 3D resolution and sensitivity over our existing HRRT (CPS Innovations, Knoxville) will allow us to address these challenging issues.